Slow But Steady: Real-World Data Supports Avacopan Use in GPA/MPA

The largest US real-world cohort to date finds avacopan reduced disease activity and glucocorticoid burden in GPA/MPA, though sustained remission rates lagged behind the ADVOCATE trial.¹

Avacopan demonstrated meaningful reductions in disease activity and glucocorticoid (GC) exposure in patients with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) in a real-world, 2-center US cohort, though sustained remission rates were lower than those reported in the ADVOCATE trial, according to a retrospective study presented at the European Alliance of Associations for Rheumatology (EULAR), held June 3-6 in London, United Kingdom.^1,2

RheumatologyLive sat down with Anisha Dua, MD, MPH, Professor of Medicine in the Division of Rheumatology and Director of the Northwestern Vasculitis Center at Northwestern University Feinberg School of Medicine, Chicago, a co-investigator on the study. The retrospective cohort included 159 avacopan initiators across Mass General Brigham and Northwestern University, with a mean (SD) age of 58.5 (17.3) years. Most patients were female (70.4%), newly diagnosed (66.7%), had GPA (57.9%), and were PR3-ANCA positive (45.9%). Median (IQR) BVAS at initiation was 8 (3, 13). Rituximab was used for remission induction in 61.0% of patients; 31.4% received both rituximab and cyclophosphamide.¹

Among 148 patients with 12-month follow-up data, BVAS = 0 was achieved by 85.8% at month 6 and 93.9% at month 12. GC-free status was achieved by 56.8% at month 6 and 80.4% at month 12. At month 12, 73 patients (49.3%) achieved sustained remission — defined as BVAS = 0 at months 6 and 12, no relapse between months 6 and 12, and no GC use within 1 month of either time point — while 96 (64.9%) achieved sustained remission permitting a prednisone-equivalent daily dose (PEDD) of ≤5 mg. Thirteen patients (8.8%) experienced 16 relapses between months 6 and 12, of which 12 (75.0%) were major; 5 relapses (31.3%) occurred after avacopan discontinuation. Median (IQR) cumulative prednisone-equivalent GC exposure fell from 2445 (1024, 4777) mg in the 12 months prior to avacopan initiation to 1199 (472, 2607) mg over the 12 months following initiation.¹

Renal outcomes were notable. Among patients with GPA/MPA-related kidney involvement (n = 71), median (IQR) eGFR increased from 39 (21, 70) mL/min/1.73 m² at initiation to 59 (36, 77) mL/min/1.73 m² at month 12. Among patients with a baseline urine protein-to-creatinine ratio (UPCR) >0.2 g/g, median UPCR declined from 1.2 (0.8, 2.7) g/g to 0.3 (0.1, 0.8) g/g, a median reduction of 73.7%. Of 12 patients on dialysis at initiation with complete follow-up data, 7 (58.3%) had discontinued dialysis by month 12.¹ Dua noted that this population — patients with more severe renal manifestations — was largely excluded from the ADVOCATE trial, making these real-world data particularly informative.

At month 12, 70 patients (47.3%) remained on avacopan. Among those who discontinued prior to month 12, the most common reason was completion of a planned treatment course (55.1%); liver test abnormalities accounted for 7.7% of discontinuations. The majority of patients (57.4%) showed no worsening of metabolic GC toxicity over 12 months.¹

On March 31, 2026, the FDA issued a Drug Safety Communication identifying serious postmarketing cases of drug-induced liver injury (DILI), including fatal cases of vanishing bile duct syndrome (VBDS), associated with avacopan. On April 30, 2026, the FDA formally proposed withdrawal of avacopan (Tavneos) from the US market, citing efficacy concerns related to trial data irregularities and the drug's hepatotoxicity risk profile. In Japan, where 20 patient deaths were reported in association with avacopan use, licensee Kissei Pharmaceutical urged physicians to halt new prescriptions in May 2026 before revising that guidance to require strict liver function monitoring per updated labeling. Avacopan remains approved and commercially available in the US and Japan while regulatory proceedings continue.^3,4,5

On liver monitoring, Dua said she checks liver enzymes every few weeks for at least the first 2 months after initiation, then spaces monitoring to every 2 to 3 months, with more frequent reassessment if fluctuations arise.

Dua highlighted that real-world GC tapering was slower than in the trial setting.² "People are maybe starting a little bit later, but at time point zero, whenever they started, they might keep — depending on the patient specifically — [them] on some dose of steroid, or hovering on a lower dose for a little bit longer period of time," she said, while noting that efficacy outcomes and the absence of new safety signals were reassuring.

Dua’s disclosures include Amgen, Abbvie, Astra Zeneca, Novartis, GSK, Sanofi, Zenas, Novartis, Rheumatology Research Foundation, Sebastian Unizony IQVIA, PTC Therapeutics, and Harvard Pilgrim Healthcare.

References

1. Patel N, Jaros B, King A, et al. One year real-world effectiveness and safety with avacopan in granulomatosis with polyangiitis and microscopic polyangiitis in two large healthcare systems. Presented at: EULAR 2026. Poster 0135

2. Jayne DRW, Merkel PA, Schall TJ, Bekker P; ADVOCATE Study Group. Avacopan for the treatment of ANCA-associated vasculitis. N Engl J Med. 2021;384(7):599–609. doi:10.1056/NEJMoa2023386

3. US Food and Drug Administration. FDA identifies cases of serious liver injury in patients taking Tavneos (avacopan). Drug Safety Communication. March 31, 2026. https://www.fda.gov/media/191708/download

4. US Food and Drug Administration, Center for Drug Evaluation and Research. ChemoCentryx, Inc.; proposal to withdraw approval of new drug application for TAVNEOS (avacopan) capsule, 10 milligrams; opportunity for a hearing. Fed Regist. 2026;91(83):23278. https://www.federalregister.gov/documents/2026/04/30/2026-08455/chemocentryx-inc-proposal-to-withdraw-approval-of-new-drug-application-for-tavneos-avacopan-capsule

5. An Important Update Regarding TAVNEOS® (avacopan). Amgen. News release. June 2, 2026. https://www.amgen.com/tavneos-prescribers